Highlights

A comprehensive battery that can test all functional domains of the CNS Provides both objective and subjective measures

Rapid retesting allows researchers to complete several rounds of testing both before and after the drug is administered

Full dose-effect curves can be measured quickly and easily

High sensitivity can robustly detect even subtleeffects

The highly flexible design can be adapted easily to meet a sponsor’s specific needs

Test data are captured automatically and entered directly into a CDIS-validated system

The tests are safe and have been used successfully for nearly three decades to test a wide range of CNS drugs

Summary

NeuroCart is a full battery of tests for measuring a wide range of CNS functions. Importantly, NeuroCart can be used to correlate a compound’s CNS effects with drug concentration, helping determine whether an effect is due to specifically the compound.

A clear advantage over other CNS test batteries is that NeuroCart provides both objective (e.g. neurophysiology) and subjective (e.g. cognitive function, memory, mood, etc.) measures of CNS function. In addition, NeuroCart is completely mobile and self-contained, including all of the necessary equipment and protocols

Practical answers to important research questions

Does our compound have the specific properties that we expect?

CHDR performed the first-in-human trials to test a short-acting benzodiazepine. Researchers used a NeuroCart test (saccadic peak velocity) and determined the dose that produced the same effect as a standard dose of midazolam. Pharmacokinetics/pharmacodynamics (PK/PD) analyses showed that the new benzodiazepine was more potent and faster acting than midazolam. Importantly, the predicted optimal dose, potency, and duration of the new compound were subsequently confirmed in clinical studies with patients.

How do we determine the optimal dose?

Because NeuroCart’s neurophysiological tests can be used as a surrogate marker for measuring a drug’s effect, these tests can be used to identify a dose that has the same effect on CNS function as the effective dose of a known compound.
For instance, CHDR recently studied a new neuroleptic D2 receptor antagonist. Using NeuroCart, and the adaptive tracking test in particular, researchers were able to determine a dose with similar potency as an effective dose of haloperidol. Importantly, although previous studies predicted an effective dose of 60 mg, NeuroCart showed that a much lower dose (10-30 mg) is effective. Clinical research in patients later confirmed that a dose as low as 5 mg dose is effective, and fewer adverse effects were reported at this lower dose compared to 60 mg.

How do we steer between effect and complications?

In some cases, preclinical research can provide evidence that a promising candidate drug may have a relatively small therapeutic index, as in the case of an ORX1/2 antagonist, a new sleep-inducing medication. Researchers worried that this new drug might induce a narcolepsy-like state, particularly at higher doses. To test this possibility, CHDR used several NeuroCart tests and found that this new compound has promising properties similar zolpidem and is safe at a dose of 1 mg. These findings were later confirmed in clinical testing

Want to know more about NeuroCart® at CHDR? Contact us

Neurology

CHDR is contributing to the development of new drugs against neurodegeneration. We are developing biomarkers to demonstrate a compound’s effects in healthy volunteers, and at the same time we are expanding our abilities to perform research in patients with Alzheimer’s disease and other neurodegenerative diseases, such as Multiple Sclerosis, Parkinson's Disease or epilepsy. CHDR’s staff includes two board-certified neurologists with clinical positions in academic medical hospitals in Leiden and Amsterdam.